The effects of lymphocyte function following brief exposure of mouse spleens to 2,3,7,8-tetrachlorodibenzodioxin (TCDD) in dimethylsulfoxide (DMSO) were studied. DNA, RNA and protein synthesis was severely inhibited at concentrations less than 10 to the minus 7th power mM TCDD per ml of DMSO when compared to DMSO treated controls. This concentration of TCDD accounted for approximately 0.14 ng TCDD uptake per spleen. The structurally related chemicals 3,4,3',4'-tetrachlorobiphenyl and NH2-2,3,7-trichlorodibenzo-p-dioxin did not show any significant lymphocytic effects even at 2-fold higher concentrations. The ability of lymphocyte mitogens to bind to cell surface receptors was not effected by TCDD treatment. Studies with mitogens specific for lymphocyte subpopulations suggested that T-lymphocytes are slightly more susceptible to TCDD-induced immunosuppression than B-lymphocytes. Treatment with DMSO alone was slightly toxic to lymphoid cells as indicated by a 10-20% loss of cell viability within 4 hrs after DMSO exposure. While this made it somewhat difficult to determine TCDD-induced cytolysis, it appears that TCDD was slightly cytolytic to lymphocytes particularly 48 hrs after exposure.